HRP20182017T4 - Antibodies that specifically bind staphylococcus aureus alpha toxin and methods of use - Google Patents

Antibodies that specifically bind staphylococcus aureus alpha toxin and methods of use Download PDF

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Publication number
HRP20182017T4
HRP20182017T4 HRP20182017TT HRP20182017T HRP20182017T4 HR P20182017 T4 HRP20182017 T4 HR P20182017T4 HR P20182017T T HRP20182017T T HR P20182017TT HR P20182017 T HRP20182017 T HR P20182017T HR P20182017 T4 HRP20182017 T4 HR P20182017T4
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Croatia
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antigen
binding fragment
antibody
seq
alpha toxin
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HRP20182017TT
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Croatian (hr)
Inventor
Bret SELLMAN
Christine TKACZYK
Lei Hua
Partha Chowdhury
Reena VARKEY
Melissa Damschroder
Li Peng
Vaheh Oganesyan
Jamese Johnson Hilliard
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Medimmune, Llc
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Application filed by Medimmune, Llc filed Critical Medimmune, Llc
Publication of HRP20182017T1 publication Critical patent/HRP20182017T1/en
Publication of HRP20182017T4 publication Critical patent/HRP20182017T4/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/40Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum bacterial
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/14Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • A61P39/02Antidotes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1271Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56911Bacteria
    • G01N33/56938Staphylococcus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2299/00Coordinates from 3D structures of peptides, e.g. proteins or enzymes
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/195Assays involving biological materials from specific organisms or of a specific nature from bacteria
    • G01N2333/305Assays involving biological materials from specific organisms or of a specific nature from bacteria from Micrococcaceae (F)
    • G01N2333/31Assays involving biological materials from specific organisms or of a specific nature from bacteria from Micrococcaceae (F) from Staphylococcus (G)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/20Dermatological disorders
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/44Multiple drug resistance
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/70Mechanisms involved in disease identification
    • G01N2800/709Toxin induced
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Claims (17)

1. Izolirano protutijelo ili njegov ulomak koji veže antigen, naznačeno time što se izolirano protutijelo ili njegov ulomak koji veže antigen imunospecifično veže na polipeptid alfa toksina koji stvara Staphylococcus aureus i sadrži: (a) VH CDR1 sadrži sekvencu aminokiseline iz SEQ ID NO: 69; (b) VH CDR2 sadrži sekvencu aminokiseline iz SEQ ID NO: 70; (c) VH CDR3 sadrži sekvencu aminokiseline iz SEQ ID NO: 71; (d) VL CDR1 sadrži sekvencu aminokiseline iz SEQ ID NO: 1; (e) VL CDR2 sadrži sekvencu aminokiseline iz SEQ ID NO: 2, i (f) VL CDR3 sadrži sekvencu aminokiseline iz SEQ ID NO: 68 .1. An isolated antibody or an antigen-binding fragment thereof, characterized in that the isolated antibody or an antigen-binding fragment thereof binds immunospecifically to the alpha toxin polypeptide produced by Staphylococcus aureus and contains: (a) VH CDR1 comprises the amino acid sequence of SEQ ID NO: 69; (b) VH CDR2 comprises the amino acid sequence of SEQ ID NO: 70; (c) VH CDR3 comprises the amino acid sequence of SEQ ID NO: 71; (d) VL CDR1 comprises the amino acid sequence of SEQ ID NO: 1; (e) VL CDR2 comprises the amino acid sequence of SEQ ID NO: 2, i (f) VL CDR3 contains the amino acid sequence of SEQ ID NO: 68. 2. Izolirano protutijelo ili ulomak koji veže antigen prema zahtjevu 1, naznačeno time što sadrži varijabilnu domenu teškog lanca koja je barem 90% identična s aminokiselinskom sekvencom iz SEQ ID NO: 57, i varijabilnu domenu laganog lanca koja je barem 90% identična sa aminokiselinskom sekvencom iz SEQ ID NO: 58.2. An isolated antibody or antigen-binding fragment according to claim 1, characterized in that it contains a heavy chain variable domain that is at least 90% identical to the amino acid sequence from SEQ ID NO: 57, and a light chain variable domain that is at least 90% identical to the amino acid sequence with the sequence from SEQ ID NO: 58. 3. Protutijelo ili ulomak koji veže antigen prema zahtjevu 2, naznačeno time što VH i VL odgovaraju sekvencama aminokiselina iz SEQ ID NO: 57 i 58.3. Antibody or antigen-binding fragment according to claim 2, characterized in that VH and VL correspond to amino acid sequences from SEQ ID NO: 57 and 58. 4. Protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 3, naznačeno time što izolirano protutijelo ili njegov ulomak koji veže antigen ima jednu ili više značajki odabranih iz skupine koju čine: (a) konstanta afiniteta (KD) za alfa toksin od oko 13 nM ili manje; (b) veže se na monomere alfa toksina, ali ne inhibira vezanje alfa toksina na receptor alfa toksina; (c) inhibira stvaranje oligomera alfa toksina za barem 50%, 60%, 70%, 80%, 90%, ili 95%; (d) smanjuje citolitičku aktivnost alfa toksina za barem 50%, 60%, 70%, 80%, 90%, ili 95% (npr.., određeno pomoću testova lize stanice i hemolize stanice); i (e) smanjuje infiltraciju stanica i pro-upalno oslobađanje citokina (npr., u modelu životinjske upale pluća).4. Antibody or antigen-binding fragment according to any one of claims 1 to 3, characterized in that the isolated antibody or antigen-binding fragment thereof has one or more features selected from the group consisting of: (a) an affinity constant (KD) for the alpha toxin of about 13 nM or less; (b) binds to alpha toxin monomers but does not inhibit alpha toxin binding to the alpha toxin receptor; (c) inhibits alpha toxin oligomer formation by at least 50%, 60%, 70%, 80%, 90%, or 95%; (d) reduces the cytolytic activity of the alpha toxin by at least 50%, 60%, 70%, 80%, 90%, or 95% (eg, determined by cell lysis and cell hemolysis assays); and (e) reduces cell infiltration and pro-inflammatory cytokine release (eg, in an animal model of lung inflammation). 5. Pripravak naznačen time što sadrži protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 4.5. A preparation characterized in that it contains an antibody or an antigen-binding fragment according to any one of claims 1 to 4. 6. Pripravak prema zahtjevu 5, naznačen time što pripravak sadrži dodatno sredstvo, pri čemu je dodatno sredstvo antibiotik.6. The preparation according to claim 5, characterized in that the preparation contains an additional agent, wherein the additional agent is an antibiotic. 7. Komplet, naznačen time što sadrži (a) protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 4 ili pripravak prema zahtjevu ili 6; (b) upute za uporabu pripravka ili smjernice za dobivanje uputa za uporabu pripravka.7. The set, indicated by what it contains (a) an antibody or antigen-binding fragment according to any of claims 1 to 4 or a preparation according to claim or 6; (b) instructions for use of the preparation or guidelines for obtaining instructions for use of the preparation. 8. Protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 4 ili pripravak prema zahtjevu 5 ili 6, naznačeno time što je za uporabu za prevenciju, liječenje ili upravljanje upalom pluća kod subjekta.8. An antibody or antigen-binding fragment according to any one of claims 1 to 4 or a composition according to claim 5 or 6, for use in the prevention, treatment or management of pneumonia in a subject. 9. Protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 4 ili pripravak prema zahtjevu 5 ili 6, naznačeno time što je za uporabu za prevenciju, liječenje ili upravljanje stanjem infekcije kože kod subjekta.9. An antibody or antigen-binding fragment according to any one of claims 1 to 4 or a composition according to claim 5 or 6, characterized in that it is for use in the prevention, treatment or management of a skin infection condition in a subject. 10. Protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 4 ili pripravak prema zahtjevu 5 ili 6, naznačeno time što je za uporabu za prevenciju, liječenje ili upravljanje upalom pluća ili stanjem infekcije kože kod subjekta prema zahtjevu 8 ili 9 inhibicijom stvaranja oligomera alfa toksina Staphylococcus aureus za barem 50%, 60%, 70%, 80%, 90% ili 95%.10. An antibody or antigen-binding fragment according to any one of claims 1 to 4 or a preparation according to claim 5 or 6, characterized in that it is for use in preventing, treating or managing pneumonia or a skin infection condition in a subject according to claim 8 or 9 by inhibiting of Staphylococcus aureus alpha toxin oligomer formation by at least 50%, 60%, 70%, 80%, 90% or 95%. 11. Protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačeno time što se imuno specifično veže na ulomak alfa toksina koji stvara Staphylococcus aureus iz SEQ ID NO: 39.11. The antibody or antigen-binding fragment according to any one of claims 1 to 4 characterized in that it immunospecifically binds to the alpha toxin fragment produced by Staphylococcus aureus of SEQ ID NO: 39. 12. Izolirano protutijelo ili ulomak koji veže antigen prema zahtjevu 11, naznačeno time što se protutijelo ili njegov ulomak koji veže antigen veže na ulomak koji sadrži aminokiseline 261-272 iz SEQ ID NO: 39 i/ili aminokiseline 173-201 iz SEQ ID NO: 39.12. Isolated antibody or antigen-binding fragment according to claim 11, characterized in that the antibody or its antigen-binding fragment binds to a fragment containing amino acids 261-272 from SEQ ID NO: 39 and/or amino acids 173-201 from SEQ ID NO : 39. 13. Izolirano protutijelo ili ulomak koji veže antigen prema zahtjevu 12, naznačeno time što se protutijelo ili njegov ulomak koji veže antigen veže se na ulomak koji sadrži aminokiseline 261-272 iz SEQ ID NO: 39 i aminokiseline 173-201 iz SEQ ID NO: 39.13. Isolated antibody or antigen-binding fragment according to claim 12, characterized in that the antibody or its antigen-binding fragment binds to a fragment containing amino acids 261-272 from SEQ ID NO: 39 and amino acids 173-201 from SEQ ID NO: 39. 14. Izolirano protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1 do 4, naznačeno time što protutijelo ili njegov ulomak koji veže antigen sprječava nastanak heptamera alfa toksina, i pri čemu je navedeno protutijelo ili ulomak koji veže antigen u kontaktu s ostacima na položajima T261, T263, N264, K266, K271, N177, W179, G180, P181, Y182, D183, D185, S186, W187, N188, P189, V190, Y191 i R200 od SEQ ID NO: 39.14. An isolated antibody or antigen-binding fragment according to any one of claims 1 to 4, characterized in that the antibody or antigen-binding fragment thereof prevents the formation of alpha toxin heptamers, and wherein said antibody or antigen-binding fragment is in contact with residues on positions T261, T263, N264, K266, K271, N177, W179, G180, P181, Y182, D183, D185, S186, W187, N188, P189, V190, Y191 and R200 of SEQ ID NO: 39. 15. Pripravak prema zahtjevu 6, naznačen time što je antibiotik vankomicin.15. The preparation according to claim 6, characterized in that the antibiotic is vancomycin. 16. Izolirano protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 11 do 14 naznačeno time što je za uporabu za prevenciju, liječenje ili upravljanje upalom pluća ili stanjem infekcije kože kod subjekta inhibicijom stvaranja oligomera alfa toksina.16. An isolated antibody or antigen-binding fragment according to any one of claims 11 to 14 for use in preventing, treating or managing a pneumonia or skin infection condition in a subject by inhibiting alpha toxin oligomer formation. 17. Izolirano protutijelo ili ulomak koji veže antigen prema bilo kojem od zahtjeva 1-4 i 11-14 koje obuhvaća varijantu Fc regije, naznačeno time što izolirano protutijelo sadrži slijedeće sekvence [image] i [image] 17. An isolated antibody or antigen-binding fragment according to any of claims 1-4 and 11-14 comprising a variant of the Fc region, characterized in that the isolated antibody contains the following sequences [image] and [image]
HRP20182017TT 2011-02-08 2018-11-29 Antibodies that specifically bind staphylococcus aureus alpha toxin and methods of use HRP20182017T4 (en)

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